{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T01:42:45Z","timestamp":1773970965184,"version":"3.50.1"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta-analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade \u22653 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade \u22653 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future.<\/jats:p>","DOI":"10.1038\/srep32020","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T09:22:10Z","timestamp":1472116930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis"],"prefix":"10.1038","volume":"6","author":[{"given":"Liang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi-Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Long","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Qiu","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nai-Qing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"BFsrep32020_CR1","first-page":"87","volume":"65","author":"LA Torre","year":"2015","unstructured":"Torre, L. A. et al. Global cancer statistics, 2012. CA: Cancer J Clin 65, 87\u2013108 (2015).","journal-title":"CA: Cancer J Clin"},{"key":"BFsrep32020_CR2","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1007\/s13277-015-3285-6","volume":"36","author":"P Madureira","year":"2015","unstructured":"Madureira, P., de Mello, R. A., de Vasconcelos, A. & Zhang, Y. Immunotherapy for lung cancer: for whom the bell tolls? Tumor Biol 36, 1411\u20131422 (2015).","journal-title":"Tumor Biol"},{"key":"BFsrep32020_CR3","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1007\/s13277-012-0465-5","volume":"33","author":"RA de Mello","year":"2012","unstructured":"de Mello, R. A. et al. EGFR exon mutation distribution and outcome in non-small-cell lung cancer: a Portuguese retrospective study. Tumour Biol 33, 2061\u20132068 (2012).","journal-title":"Tumour Biol"},{"key":"BFsrep32020_CR4","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.3892\/etm.2014.1574","volume":"7","author":"M Zhao","year":"2014","unstructured":"Zhao, M., Li, H., Li, L. & Zhang, Y. Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients. Exp Ther Med 7, 1403\u20131407 (2014).","journal-title":"Exp Ther Med"},{"key":"BFsrep32020_CR5","doi-asserted-by":"crossref","unstructured":"Wakelee, H., Kelly, K. & Edelman, M. J. 50 Years of progress in the systemic therapy of non-small cell lung cancer. Am Soc Clin Oncol Educ Book 177\u2013189 (2014).","DOI":"10.14694\/EdBook_AM.2014.34.177"},{"key":"BFsrep32020_CR6","doi-asserted-by":"publisher","first-page":"e32695","DOI":"10.1371\/journal.pone.0032695","volume":"7","author":"J Wang","year":"2012","unstructured":"Wang, J. et al. Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials. PLoS One 7, e32695 (2012).","journal-title":"PLoS One"},{"key":"BFsrep32020_CR7","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1189\/jlb.0313121","volume":"94","author":"F McCarthy","year":"2013","unstructured":"McCarthy, F., Roshani, R., Steele, J. & Hagemann, T. Current clinical immunotherapy targets in advanced nonsmall cell lung cancer (NSCLC). J Leukocyte Biol 94, 1201 (2013).","journal-title":"J Leukocyte Biol"},{"key":"BFsrep32020_CR8","doi-asserted-by":"crossref","unstructured":"Brahmer, J. R. et al. KEYNOTE-024: Phase III trial of pembrolizumab (MK-3475) vs. platinum-based chemotherapy as first-line therapy for patients with metastatic non-small cell lung cancer (NSCLC) that expresses programmed cell death ligand 1 (PD-L1). J Clin Oncol 33, (suppl; abstr 8103) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.tps8103"},{"key":"BFsrep32020_CR9","doi-asserted-by":"crossref","unstructured":"Planchard, D. et al. A phase III study of MEDI4736 (M), an anti-PD-L1 antibody, in monotherapy or in combination with Tremelimumab (T), versus standard of care (SOC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) who have received at least two prior systemic treatment regimens (ARCTIC). J Clin Oncol 33, (suppl; abstr 8104) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.tps8104"},{"key":"BFsrep32020_CR10","doi-asserted-by":"crossref","unstructured":"Mok, T. et al. Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1-positive advanced non-small cell lung cancer (NSCLC). J Clin Oncol 33, (suppl; abstr 8105) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.tps8105"},{"key":"BFsrep32020_CR11","doi-asserted-by":"crossref","unstructured":"Gulley, J. L. et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: A phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy. J Clin Oncol 33, (suppl; abstr 8034) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.8034"},{"key":"BFsrep32020_CR12","doi-asserted-by":"crossref","unstructured":"Nishio, M. et al. Phase II studies of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced squamous (sq) or nonsquamous (non-sq) non-small cell lung cancer (NSCLC). J Clin Oncol 33, (suppl; abstr 8027) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.8027"},{"key":"BFsrep32020_CR13","doi-asserted-by":"crossref","unstructured":"Carbone, D. P. et al. A phase III, randomized, open-label trial of nivolumab (anti-PD-1; BMS-936558, ONO-4538) versus investigator\u2019s choice chemotherapy (ICC) as first-line therapy for stage IV or recurrent PD-L1+ non-small cell lung cancer (NSCLC). J Clin Oncol 32, (suppl; abstr 8128) (2014).","DOI":"10.1200\/jco.2014.32.15_suppl.tps8128"},{"key":"BFsrep32020_CR14","doi-asserted-by":"crossref","unstructured":"Bazhenova, L. et al. An international, multicenter, randomized, double-blind phase III study of maintenance belagenpumatucel-l in non-small cell lung cancer (NSCLC): Updated analysis of patients enrolled within 12 weeks of completion of chemotherapy. J Clin Oncol 32, (suppl; abstr 8056) (2014).","DOI":"10.1200\/jco.2014.32.15_suppl.8056"},{"key":"BFsrep32020_CR15","doi-asserted-by":"crossref","unstructured":"Govindan, R., Morris, J. C., Rossi, G. R., Vahanian, N. N. & Link, C. J. NLG-0301: An open-label, randomized phase 2B active control study of second-line tergenpumatucel-L immunotherapy versus docetaxel in patients with progressive or relapsed non-small cell lung cancer (NSCLC). J Clin Oncol 32, (suppl; abstr 8133) (2014).","DOI":"10.1200\/jco.2014.32.15_suppl.tps8133"},{"key":"BFsrep32020_CR16","doi-asserted-by":"crossref","unstructured":"Reck, M. et al. CA184-104: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) with paclitaxel\/carboplatin (PC) versus placebo with PC in patients (pts) with stage IV\/recurrent non-small cell lung cancer (NSCLC) of squamous histology. J Clin Oncol 31, (suppl; abstr 8117) (2013).","DOI":"10.1200\/jco.2013.31.15_suppl.tps8117"},{"key":"BFsrep32020_CR17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1056\/NEJMoa1504627","volume":"373","author":"J Brahmer","year":"2015","unstructured":"Brahmer, J. et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 373, 123\u2013135 (2015).","journal-title":"N Engl J Med"},{"key":"BFsrep32020_CR18","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1158\/1078-0432.CCR-13-0731","volume":"20","author":"PM Forde","year":"2014","unstructured":"Forde, P. M., Kelly, R. J. & Brahmer, J. R. New strategies in lung cancer: translating immunotherapy into clinical practice. Clin Cancer Res 20, 1067\u20131073 (2014).","journal-title":"Clin Cancer Res"},{"key":"BFsrep32020_CR19","doi-asserted-by":"publisher","first-page":"364","DOI":"10.4103\/1008-682X.122585","volume":"16","author":"BH Singh","year":"2014","unstructured":"Singh, B. H. & Gulley, J. L. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications. Asian J Androl 16, 364\u2013371 (2014).","journal-title":"Asian J Androl"},{"key":"BFsrep32020_CR20","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1097\/JTO.0b013e3182156250","volume":"6","author":"R Digumarti","year":"2011","unstructured":"Digumarti, R. et al. A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer. J Thorac Oncol 6, 1098\u20131103 (2011).","journal-title":"J Thorac Oncol"},{"key":"BFsrep32020_CR21","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.1200\/JCO.2010.34.4127","volume":"29","author":"PM Parikh","year":"2011","unstructured":"Parikh, P. M. et al. Randomized, Double-Blind, Placebo-Controlled Phase II Study of Single-Agent Oral Talactoferrin in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer That Progressed After Chemotherapy. J Clin Oncol 29, 4129\u20134136 (2011).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR22","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1093\/annonc\/mdt371","volume":"24","author":"S Ramalingam","year":"2013","unstructured":"Ramalingam, S. et al. Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial). Ann Oncol 24, 2875\u20132880 (2013).","journal-title":"Ann Oncol"},{"key":"BFsrep32020_CR23","doi-asserted-by":"publisher","first-page":"156","DOI":"10.2522\/ptj.20070147","volume":"88","author":"SA Olivo","year":"2008","unstructured":"Olivo, S. A. et al. Scales to assess the quality of randomized controlled trials: a systematic review. Phys Ther 88, 156\u2013175 (2008).","journal-title":"Phys Ther"},{"key":"BFsrep32020_CR24","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.1002\/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8","volume":"17","author":"MK Parmar","year":"1998","unstructured":"Parmar, M. K., Torri, V. & Stewart, L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17, 2815\u20132834 (1998).","journal-title":"Stat Med"},{"key":"BFsrep32020_CR25","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1745-6215-8-16","volume":"8","author":"JF Tierney","year":"2007","unstructured":"Tierney, J. F., Stewart, L. A., Ghersi, D., Burdett, S. & Sydes, M. R. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8, 16 (2007).","journal-title":"Trials"},{"key":"BFsrep32020_CR26","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557\u2013560 (2003).","journal-title":"BMJ"},{"key":"BFsrep32020_CR27","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1200\/JCO.2007.11.5980","volume":"26","author":"VE Neninger","year":"2008","unstructured":"Neninger, V. E. et al. Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. J Clin Oncol 26, 1452\u20131458 (2008).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR28","doi-asserted-by":"publisher","first-page":"3979","DOI":"10.1200\/JCO.2007.12.5807","volume":"26","author":"C Manegold","year":"2008","unstructured":"Manegold, C. et al. Randomized Phase II Trial of a Toll-Like Receptor 9 Agonist Oligodeoxynucleotide, PF-3512676, in Combination With First-Line Taxane Plus Platinum Chemotherapy for Advanced-Stage Non-Small-Cell Lung Cancer. J Clin Oncol 26, 3979\u20133986 (2008).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR29","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1007\/s00432-011-1003-3","volume":"137","author":"C Butts","year":"2011","unstructured":"Butts, C. et al. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin 137, 1337\u20131342 (2011).","journal-title":"J Cancer Res Clin"},{"key":"BFsrep32020_CR30","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/S1470-2045(11)70259-5","volume":"12","author":"E Quoix","year":"2011","unstructured":"Quoix, E. et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial. Lancet Oncol 12, 1125\u20131133 (2011).","journal-title":"Lancet Oncol"},{"key":"BFsrep32020_CR31","doi-asserted-by":"crossref","unstructured":"Shtivelband, M. et al. Randomized, blinded, placebo-controlled phase II trial of docetaxel and bavituximab as second-line therapy in locally advanced or metastatic non-squamous non-small cell lung cancer. J Clin Oncol 31, (suppl; abstr 8095) (2013).","DOI":"10.1200\/jco.2013.31.15_suppl.8095"},{"key":"BFsrep32020_CR32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S1470-2045(13)70510-2","volume":"15","author":"C Butts","year":"2014","unstructured":"Butts, C. et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol 15, 59\u201368 (2014).","journal-title":"Lancet Oncol"},{"key":"BFsrep32020_CR33","doi-asserted-by":"publisher","first-page":"3660","DOI":"10.1158\/1078-0432.CCR-13-1674","volume":"20","author":"S Alfonso","year":"2014","unstructured":"Alfonso, S. et al. A Randomized, Multicenter, Placebo-Controlled Clinical Trial of Racotumomab-Alum Vaccine as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. Clin Cancer Res 20, 3660\u20133671 (2014).","journal-title":"Clin Cancer Res"},{"key":"BFsrep32020_CR34","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1016\/j.ejca.2015.07.035","volume":"51","author":"G Giaccone","year":"2015","unstructured":"Giaccone, G. et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur J Cancer 51, 2321\u20132329 (2015).","journal-title":"Eur J Cancer"},{"key":"BFsrep32020_CR35","doi-asserted-by":"crossref","unstructured":"EA, Q. et al. Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy. J Clin Oncol 33, (suppl; abstr 3034) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.3034"},{"key":"BFsrep32020_CR36","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1200\/JCO.2011.38.4032","volume":"30","author":"TJ Lynch","year":"2012","unstructured":"Lynch, T. J. et al. Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB\/IV Non-Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study. J Clin Oncol 30, 2046\u20132054 (2012).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR37","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","volume":"373","author":"H Borghaei","year":"2015","unstructured":"Borghaei, H. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 373, 1627\u20131639 (2015).","journal-title":"N Engl J Med"},{"key":"BFsrep32020_CR38","doi-asserted-by":"crossref","unstructured":"Spira, A. I. et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs. docetaxel in 2L\/3L NSCLC (POPLAR). J Clin Oncol 33, (suppl; abstr 8010) (2015).","DOI":"10.1200\/jco.2015.33.15_suppl.8010"},{"key":"BFsrep32020_CR39","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1093\/annonc\/mdh220","volume":"15","author":"MER O\u2019Brien","year":"2004","unstructured":"O\u2019Brien, M. E. R. SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results. Ann Oncol 15, 906\u2013914 (2004).","journal-title":"Ann Oncol"},{"key":"BFsrep32020_CR40","first-page":"1011","volume":"39","author":"L Ridolfi","year":"2011","unstructured":"Ridolfi, L. et al. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial. Int J Oncol 39, 1011\u20131017 (2011).","journal-title":"Int J Oncol"},{"key":"BFsrep32020_CR41","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1007\/s00262-011-1060-0","volume":"60","author":"R Zhong","year":"2011","unstructured":"Zhong, R., Teng, J., Han, B. & Zhong, H. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immun 60, 1497\u20131502 (2011).","journal-title":"Cancer Immunol Immun"},{"key":"BFsrep32020_CR42","first-page":"3997","volume":"28","author":"C Wu","year":"2008","unstructured":"Wu, C., Jiang, J., Shi, L. & Xu, N. Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer. Anticancer Res 28, 3997\u20134002 (2008).","journal-title":"Anticancer Res"},{"key":"BFsrep32020_CR43","doi-asserted-by":"publisher","first-page":"S164","DOI":"10.1097\/JTO.0b013e318174e9a7","volume":"3","author":"PA Bradbury","year":"2008","unstructured":"Bradbury, P. A. & Shepherd, F. A. Immunotherapy for lung cancer. J Thorac Oncol 3, S164\u2013S170 (2008).","journal-title":"J Thorac Oncol"},{"key":"BFsrep32020_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11912-014-0400-6","volume":"16","author":"R Ruiz","year":"2014","unstructured":"Ruiz, R., Hunis, B. & Raez, L. E. Immunotherapeutic Agents in Non-small-cell Lung Cancer Finally Coming to the Front Lines. Curr Oncol Rep 16, 1\u201310 (2014).","journal-title":"Curr Oncol Rep"},{"key":"BFsrep32020_CR45","doi-asserted-by":"publisher","first-page":"4721","DOI":"10.1200\/JCO.2005.05.5335","volume":"24","author":"J Nemunaitis","year":"2006","unstructured":"Nemunaitis, J. et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol 24, 4721\u20134730 (2006).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR46","doi-asserted-by":"publisher","first-page":"145","DOI":"10.4161\/cbt.5.2.2334","volume":"5","author":"T Crombet Ramos","year":"2006","unstructured":"Crombet Ramos, T. et al. Treatment of NSCLC Patients with an EGF-Based Cancer Vaccine. Cancer Biol Ther 5, 145\u2013149(2006).","journal-title":"Cancer Biol Ther"},{"key":"BFsrep32020_CR47","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/CJI.0b013e31818fe167","volume":"32","author":"E Neninger","year":"2009","unstructured":"Neninger, E. et al. Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer. J Immunother 32, 92\u201399 (2009).","journal-title":"J Immunother"},{"key":"BFsrep32020_CR48","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","volume":"12","author":"DM Pardoll","year":"2012","unstructured":"Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12, 252\u2013264 (2012).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep32020_CR49","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1097\/CCO.0000000000000167","volume":"27","author":"C Helissey","year":"2015","unstructured":"Helissey, C., Champiat, S. & Soria, J. Immune checkpoint inhibitors in advanced nonsmall cell lung cancer. Curr Opin Oncol 27, 108\u2013117 (2015).","journal-title":"Curr Opin Oncol"},{"key":"BFsrep32020_CR50","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","volume":"366","author":"SL Topalian","year":"2012","unstructured":"Topalian, S. L. et al. Safety, activity and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366, 2443\u20132454 (2012).","journal-title":"N Engl J Med"},{"key":"BFsrep32020_CR51","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1097\/00002371-200111000-00007","volume":"24","author":"A Marten","year":"2001","unstructured":"Marten, A. et al. Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations. J Immunother 24, 502\u2013510 (2001).","journal-title":"J Immunother"},{"key":"BFsrep32020_CR52","doi-asserted-by":"publisher","first-page":"914","DOI":"10.3390\/toxins6030914","volume":"6","author":"L Gelao","year":"2014","unstructured":"Gelao, L., Criscitiello, C., Esposito, A., Goldhirsch, A. & Curigliano, G. Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an \u201cInnocent Bystander\u201d. Toxins 6, 914\u2013933 (2014).","journal-title":"Toxins"},{"key":"BFsrep32020_CR53","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1200\/JCO.2014.60.0379","volume":"33","author":"JS Weber","year":"2015","unstructured":"Weber, J. S., Yang, J. C., Atkins, M. B. & Disis, M. L. Toxicities of Immunotherapy for the Practitioner. J Clin Oncol 33, 2092\u20132099 (2015).","journal-title":"J Clin Oncol"},{"key":"BFsrep32020_CR54","first-page":"e6321","volume":"5","author":"M Wang","year":"2015","unstructured":"Wang, M. et al. Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis. BMJ Open 5, e6321 (2015).","journal-title":"BMJ Open"},{"key":"BFsrep32020_CR55","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.intimp.2015.05.021","volume":"28","author":"S Wang","year":"2015","unstructured":"Wang, S. & Wang, Z. Efficacy and safety of dendritic cells co-cultured with cytokine-induced killer cells immunotherapy for non-small-cell lung cancer. Int Immunopharmacol 28, 22\u201328 (2015).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep32020_CR56","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.3109\/14653240903121252","volume":"11","author":"H Li","year":"2009","unstructured":"Li, H. et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy 11, 1076\u20131083 (2009).","journal-title":"Cytotherapy"},{"key":"BFsrep32020_CR57","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.3892\/etm.2014.1574","volume":"7","author":"M Zhao","year":"2014","unstructured":"Zhao, M., Li, H., Li, L. & Zhang, Y. Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients. Exp Ther Med 7, 1403\u20131407 (2014).","journal-title":"Exp Ther Med"},{"key":"BFsrep32020_CR58","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1097\/CJI.0000000000000015","volume":"37","author":"SB Shi","year":"2014","unstructured":"Shi, S. B. et al. Efficacy of erlotinib plus dendritic cells and cytokine-induced killer cells in maintenance therapy of advanced non-small cell lung cancer. J Immunother 37, 250\u2013255 (2014).","journal-title":"J Immunother"},{"key":"BFsrep32020_CR59","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1177\/030089161209800306","volume":"98","author":"SB Shi","year":"2012","unstructured":"Shi, S. B., Ma, T. H., Li, C. H. & Tang, X. Y. Effect of maintenance therapy with dendritic cells: cytokine-induced killer cells in patients with advanced non-small cell lung cancer. Tumori 98, 314\u2013319 (2012).","journal-title":"Tumori"},{"key":"BFsrep32020_CR60","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00262-012-1311-8","volume":"62","author":"L Yang","year":"2013","unstructured":"Yang, L. et al. Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients. Cancer Immunol Immun 62, 65\u201373 (2013).","journal-title":"Cancer Immunol Immun"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32020","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32020.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32020.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T21:12:01Z","timestamp":1672866721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,25]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,10,17]]}},"alternative-id":["BFsrep32020"],"URL":"https:\/\/doi.org\/10.1038\/srep32020","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,25]]},"assertion":[{"value":"22 December 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32020"}}